title: Design, synthesis, and evaluation of novel 3,6-diaryl-4-aminoalkoxyquinolines as selective agonists of somatostatin receptor subtype 2.
abstract: Agonists of somatostatin receptor subtype 2 (sst(2)) have been proposed as therapeutics for the treatment of proliferative diabetic retinopathy and exudative age-related macular degeneration. An HTS screen identified 2-quinolones as weak agonists of sst(2), and these were optimized to provide small molecules with sst(2) binding and functional potency comparable to peptide agonists. Agonist 21 was shown to inhibit rat growth hormone secretion following systemic administration and to inhibit ocular neovascular lesion formation after local administration.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, Sumneytown Pike, P.O. Box 4, West Point, Pennsylvania 19486, United States. scott_wolkenberg@merck.com
authors.forename: Scott E
authors.initials: SE
authors.lastname: Wolkenberg
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Zhao
authors.forename: Catherine
authors.initials: C
authors.lastname: Thut
authors.forename: Jill W
authors.initials: JW
authors.lastname: Maxwell
authors.forename: Terrence P
authors.initials: TP
authors.lastname: McDonald
authors.forename: Fumi
authors.initials: F
authors.lastname: Kinose
authors.forename: Michael
authors.initials: M
authors.lastname: Reilly
authors.forename: Craig W
authors.initials: CW
authors.lastname: Lindsley
authors.forename: George D
authors.initials: GD
authors.lastname: Hartman
mesh_terms: D000818:Animals; D016466:CHO Cells; D020256:Choroidal Neovascularization / Q000188:drug therapy; D006224:Cricetinae; D003412:Cricetulus; D004285:Dogs; D015195:Drug Design; D005260:Female; D006801:Humans; D008297:Male; D011804:Quinolines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017481:Receptors, Somatostatin / Q000819:agonists*; D013379:Substrate Specificity
chemical_list: D011804:Quinolines; D017481:Receptors, Somatostatin; C093733:somatostatin receptor 2